Urolithin A mitigates behavioral and synaptic deficits associated with epilepsy through VDAC-1 inhibition: A novel treatment approach

Supplementation of Urolithin-A, a catabolite of ellagic acid-containing precursors, has been shown to benefit the central nervous system (CNS). This study focused on deciphering the potential anti-epileptic effects of Urolithin-A, a small molecule of natural origin. To understand the primary underlying mediators of UA's anti-epileptic efficacy, RNA sequencing was performed in the sub-acute epileptic model of Drosophila (4 hours of treatment duration with epileptic inducer-picrotoxin (PTX)) to abstain from the interference of secondary pathways. Four treatment groups were included in the study: 1) Vehicle (0.5% DMSO), 2) 1mM PTX, 3) 1mM PTX + Urolithin-A (100µM), and 4) Urolithin-A (100µM). Administration of Urolithin-A restores the PTX-induced misregulated genes of brain hemolymph and metabolic dysfunctions. Overall design: The picrotoxin-induced sub-acute seizure model of Drosophila was included in the study. The sub-acute name is given according to the short treatment duration of 4 hours. Four treatment groups were included in the study: 1) Vehicle (0.5% DMSO), 2) 1mM PTX, 3) 1mM PTX + Urolithin-A (100µM), and 4) Urolithin-A (100µM). PTX represents the epileptic context.